The present invention relates to an insect-repelling agent containing N,N-diethyl-m-toluamide (DEET) based on alcohol solutions as the active ingredient (repellent), and an adjuvant that extends the period of effectiveness of DEET following application to human skin.
An insect-repelling agent of this kind is known from EP 0 090 288 B1.
DEET (N,N-diethyl-m-toluamide) is a known and proven insect-repelling agent (called a xe2x80x9crepellentxe2x80x9d).
In known insect-repelling agents, DEET is present as an alcohol solution. When an alcohol solution of this kind is applied to the skin, the period of effectiveness is about 5 hours.
For a desirably long effectiveness in the range from 6 to 8 hours following application to human skin, adjuvants that extend the period of effectiveness have been discovered.
In the context of EP 0 090 288 cited above, it was found that by adding the adjuvant polyethylene glycol 400 (PEG-400), it was possible to achieve greatly reduced resorption and an improved period of effectiveness of the actual active ingredient, i.e. the DEET repellent. The polyethylene glycol 400 adjuvant itself possesses no repellent effect. By adding the PEG-400 adjuvant to alcohol solutions of DEET, it was possible to increase the period of effectiveness. For example, the period of effectiveness of 20% DEET in isopropanol was increased from 5.7 to 7.4 hours by adding 20% PEG-400. EP 0 090 288 has also disclosed the use of univalent or polyvalent alcohols, e.g. including glycerol, as solvents. One exemplary embodiment describes a formulation made up of 15 parts DEET as active ingredient (repellent), 13 parts PEG-400 as adjuvant to extend the period of effectiveness, and a mixture of 10 parts glycerol, 8 parts water, and 53 parts isopropanol as solvent.
It has now been found, in the practical use of such insect-repelling agents, that a period of effectiveness in the range of 7 to 8 hours is not sufficient to achieve an effect that lasts an entire day.
In the summer months in particular, in which insects are a problem, the days are substantially more than 8 hours long, i.e. the period during which a person is exposed to insects in the course of a day is substantially longer than 8 hours. The result is that an insect-repelling effect cannot be achieved for an entire day with one application per day, for example in the morning, of such an insect-repelling agent.
The use of higher concentrations of DEET or the use of higher concentrations of the PEG-400 adjuvant that extends the period of effectiveness either did not produce any substantial improvement, or the disadvantages associated therewith rule out such increases.
According to the monograph xe2x80x9cDiethyltoluamidxe2x80x9d [Diethyltoluamide] (Bundesanzeiger No. 137, Jul. 23, 1994), blistering, ulceration, and necroses can occur as side effects at concentrations of DEET exceeding 30%.
Contact allergies can occasionally occur with polyethylene glycols, especially with the liquid polyethylene glycols PEG-200 to -400 (A. Zesch, Externa, Springer Verlag 1980).
In addition, polyethylene glycols exhibit the following undesirable reactions, i.e. they form peroxides when exposed to oxygen or air; react with substances that contain phenolic OH-groups, such as cresols, tannins, resorcin, or salicylic acid; and exhibit discoloration with sulfonamides, anthrasol, chrysarobin, or theophylline.
PEG""s moreover cause inactivation of certain antibiotics and preservatives, for example penicillins and p-hydroxybenzoates. PEG""s also cause dissolution of plastics such as polyethylene, PVC, and cellulose esters (Sucker et al., Pharm. Technologie, 2nd ed. 1991).
These reactions with PEG""s result in a chemical change that can impair the effectiveness and shelf life of the insect-repelling agent, cause visible discoloration of skin areas to which the insect-repelling agent is applied, and possibly adversely affect other agents applied to or contained in the skin, for example antibiotics or preservatives.
It is common practice in the summer months to use sunscreens that contain, for example, preservatives. If the PEG then reacts with a preservative of a sunscreen, the latter exhibits decomposition phenomena that result not only in loss of effectiveness but often also in an unpleasant odor. If the repellent is applied to a skin area that has been coated with antibiotics because of an injury, adverse effects (inactivation) can occur.
Against this background, it is the object of the present invention to equip an insect-repelling agent of the kind cited initially with an adjuvant that on the one hand considerably extends the period of effectiveness of DEET, and on the other hand is tolerated by human skin without interactions and also does not participate in any undesirable reactions.
According to the present invention, the object is achieved in that the sole adjuvant for extending the period of effectiveness is glycerol in an amount of more than 10 percent by weight of the insect-repelling agent.
Intensive investigations have revealed, surprisingly, that glycerol is usable as an adjuvant that effectively extends the period of effectiveness of DEET.
It is possible to replace the PEG-400 adjuvant with glycerol, so that glycerol can be used as the only and exclusive adjuvant extending the period of effectiveness of DEET.
This effect may be regarded as surprising especially because, despite the known use of glycerol as a solvent, efforts have been made in the existing art to find other adjuvants that extend the period of effectiveness of DEET, leading to the PEG-400 adjuvant in the case of the aforementioned EP 0 090 288. It is therefore to be considered surprising that glycerol can be used as the only and thus exclusive adjuvant for extending the period of effectiveness of alcohol-based DEET formulations.
Glycerol is a natural substance that occurs in human metabolism. In dermatology, glycerol is used as an additive for the care of irritated, brittle dry skin. Glycerol causes absolutely no contact allergies even in highly sensitive allergic persons, so that it can be used even by such sensitive persons. It is to be expected that insect-repelling agents of this kind will be used mostly during the vacation season, in which users are in an unfamiliar environment and extensively exposed to mosquitoes as well as usually to higher temperatures with intensive solar radiation. Persons with sensitive skin then react to additional agents applied to the skin, for example an insect-repelling agent, with allergic reactions.
Intensive investigations have shown that when glycerol is the adjuvant of an insect-repelling agent, such reactions do not occur. The reactions mentioned earlierxe2x80x94namely peroxide formation when exposed to oxygen and air, reactions with substances that contain phenolic OH groups, discoloration with sulfonamides, and inactivation of antibiotics or preservativesxe2x80x94also do not occur when glycerol is the adjuvant.
The result is not only to make available a highly skin-compatible adjuvant, but also to create the possibility of using it at relatively high concentrations, which results in a further increase in the period of effectiveness without triggering undesirable side effects due to the increased concentration.
It is to be regarded as an even more surprising effect of the replacement of PEG-400 with glycerol that, given comparable quantities of effective ingredient (DEET) and comparable quantities of adjuvant, the period of effectiveness of an insect-repelling agent can be increased to as much as 13 hours with the glycerol adjuvant. The result is thus an increase of 7 hours over the usual period of effectiveness without adjuvants, and of a further 5 hours as compared to the PEG-400 adjuvant.
The overall result is to yield a substantial increase in the period of effectiveness while at the same time reducing or preventing the occurrence of side effects, in particular allergic reactions and reactions with environmental substances or with natural substances contained in the skin or other substances applied to it.
The proportion of glycerol can be up to 60 wt %; it is preferably 20 to 50 wt %.
An optimum extension of the period of effectiveness is achieved in this preferred range: the period of effectiveness is up to 13 hours, i.e. a continuous insect-repelling effect can be obtained, even over a very long and sunny summer day, with a single application in the morning.
In a further embodiment of the invention, the proportion of DEET is 15 to 25 wt %.
The advantage of this feature is that it is possible to work with a quantity of active ingredient (repellent) that on the one hand is sufficient to produce optimum effectiveness over the long term, but at the same time represents a sufficiently small quantity that side effects described in the monographxe2x80x94such as blistering, ulceration, and necrosesxe2x80x94are ruled out.
In a further embodiment of the invention, further repellents are contained in the insect-repelling agent.
This feature, known per se, has the advantage that in particular cases in which the effectiveness of DEET must be assisted because of local or other conditions, further repellents can be utilized.
In a further embodiment of the invention, additives selected from the group comprising perfume oils, fragrances, skin-care substances, water, emulsifiers, and propellants are present.
The advantage of this feature is that by way of the additives it is possible to make available formulations that are pleasant to the skin, or particular galenical presentations can be offered, for example skin sprays, lotions, cremes, or sticks.
The use according to the present invention of glycerol as the adjuvant that extends the period of effectiveness in an insect-repelling agent thus results in an extension of the period of effectiveness with relatively small quantities of actual active ingredient (repellent), thus creating an effective and at the same time tolerable insect-repelling agent.
It is understood that the features mentioned above and those yet to be explained below can be used not only in the combinations indicated, but also in other combinations or in isolation, without leaving the context of the present invention.